Endogenous opiate peptides have been found in an area of the limbic system known to be involved in copulation. In men, use of opiate drugs can cause severe sexual dysfunction. We therefore investigated the role of the endogenous opiates in sexual function by using a convenient animal model to (1) assay for changes in plasma beta-endorphin during copulation, and (2) analyze the effects of opiate agonists and antagonists on mating behavior. Radioimmunoassay of plasma extracts revealed beta-endorphin to be at least 86 times higher in males that had just experienced their fifth ejaculation than in unmated males. Levels following a non-ejaculatory intromission, occurring after the fifth ejaculation, were at least three times higher than those of unmated males. In another experiment, both methadone and naltrexone were found to cause a dose dependent reduction in libido, with the methadone effect being the more severe. Potency (ability to achieve erection and intromission) was greatly reduced by methadone but was significantly improved by naltrexone. Pretreatment with naltrexone blocked the effects of methadone; posttreatment reversed the effects.